9-116699833-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012210.4(TRIM32):c.*129C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 1,250,184 control chromosomes in the GnomAD database, including 532,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (67178 hom., cov: 32)
  • Exomes 𝑓: 0.92 (465375 hom.)
• Consequence: TRIM32 NM_012210.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.764

Genes affected

TRIM32 (HGNC:16380): (tripartite motif containing 32) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes. [provided by RefSeq, Jul 2008]

ASTN2 (HGNC:17021): (astrotactin 2) This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 9-116699833-C-T is Benign according to our data. Variant chr9-116699833-C-T is described in ClinVar as [Benign]. Clinvar id is 364723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-116699833-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM32	NM_012210.4	c.*129C>T		3_prime_UTR_variant	2/2	ENST00000450136.2
ASTN2	NM_001365068.1	c.2806+25938G>A		intron_variant		ENST00000313400.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM32	ENST00000450136.2	c.*129C>T		3_prime_UTR_variant	2/2	1	NM_012210.4	P1
ASTN2	ENST00000313400.9	c.2806+25938G>A		intron_variant		5	NM_001365068.1	A2

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142862 AN: 152184 Hom.: 67123 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.938

GnomAD4 exome AF: 0.920 AC: 1010442 AN: 1097882 Hom.: 465375 Cov.: 14 AF XY: 0.921 AC XY: 510048 AN XY: 553862

Gnomad4 AFR exome AF: 0.979

Gnomad4 AMR exome AF: 0.940

Gnomad4 ASJ exome AF: 0.939

Gnomad4 EAS exome AF: 0.970

Gnomad4 SAS exome AF: 0.935

Gnomad4 FIN exome AF: 0.963

Gnomad4 NFE exome AF: 0.911

Gnomad4 OTH exome AF: 0.924

GnomAD4 genome AF: 0.939 AC: 142975 AN: 152302 Hom.: 67178 Cov.: 32 AF XY: 0.941 AC XY: 70059 AN XY: 74460

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.935

Alfa AF: 0.921 Hom.: 69459

Bravo AF: 0.938

Asia WGS AF: 0.943 AC: 3276 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Sarcotubular myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Bardet-Biedl syndrome 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	8.6
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3019; hg19: chr9-119462112;